1,2-Dichlorobenzene → 3-Fluoro-5-nitrobenzoic acid

HRID 341891Notes

Reaction equation

HRID 341891 reaction equation
[F:1][B-](F)(F)F.N#[O+].N[C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=1)[C:12]([OH:14])=[O:13].ClC1C=CC=CC=1Cl>C(#N)C>[F:1][C:9]1[CH:10]=[C:11]([CH:15]=[C:16]([N+:18]([O-:20])=[O:19])[CH:17]=1)[C:12]([OH:14])=[O:13]

Participants

5

Reactant 3

HCID 72391,2-DichlorobenzeneHCID 2393423-Amino-5-nitrobenzoic acidHCID 11137142Nitrilooxonium tetrafluoroborate

Product 1

HCID 27590473-Fluoro-5-nitrobenzoic acidYield 64.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A vigorously stirred slurry of nitrosonium tetrafluoroborate (3.53 g, 30.2 mM) in acetonitrile (50 ml) under an atmosphere of argon was cooled in an ice bath, and 3-amino-5-nitrobenzoic acid (5.0 g, 27.5 mM) was added in three portions. The temperature was then allowed to rise to ambient, and the mixture was stirred for 48 hours. 1,2-Dichlorobenzene (50 ml) was added, and acetonitrile distilled from the mixture at reduced pressure. The mixture was then heated to 170° for 30 minutes, when gas evolution had ended. After cooling, the mix was poured into dichloromethane (200 ml), and extracted with NaHCO3 solution. After back washing the aqueous phase with dichloromethane, it was acidified (2M hydrochloric acid), and organics extracted with ethyl acetate (2×100 ml). The combined organic layers were washed with brine, and dried over MGgSO4. Crude product was purified by chromatography on silica, eluting with a gradient from dichloromethane/acetic acid (99:1) to dichloromethane/isopropanol/acetic acid (80:20:1), to give 3-fluoro-5-nitrobenzoic acid (3.26 g, 64%). Nmr (DMSO-d6): δ 8.14 (dm, 1H); 8.37 (dt, 1H); 8.46 (m, 1H).

Workup

  1. distillationacetonitrile distilled from the mixture at reduced pressure
  2. temperatureThe mixture was then heated to 170° for 30 minutes
  3. temperatureAfter cooling
  4. additionthe mix was poured into dichloromethane (200 ml)
  5. extractionextracted with NaHCO3 solution
  6. washAfter back washing the aqueous phase with dichloromethane, it
  7. extractionorganics extracted with ethyl acetate (2×100 ml)
  8. washThe combined organic layers were washed with brine
  9. customdried over MGgSO4
  10. customCrude product was purified by chromatography on silica
  11. washeluting with a gradient from dichloromethane/acetic acid (99:1) to dichloromethane/isopropanol/acetic acid (80:20:1)

Sources & evidence

ORD record
ord-698752fc08c742d89432d26bd4f994dd
Source dataset
uspto-grants-1999_01
Patent number
US05856321

Reaction notes

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